The role of C-reactive protein as a prognostic marker in COVID-19
Dominic Stringer, Philip Braude, Phyo Kyaw Myint, Louis Evans, Jemima Collins, Alessia Verduri, Terry J Quinn, Arturo Vilches‐Moraga, Michael Stechman, Lyndsay Pearce, Susan Moug, Kathryn McCarthy, Jonathan Hewitt, Ben Carter, COPE Study Collaborators, Eilidh Bruce, Alice Einarsson, Aine McGovern, Carly Bisset, Ross Alexander, Giovanni Guaraldi, Caroline Murphy, J. Daniel Kelly, Tarik El Jichi Mutasem, Sandeep Singh, Dolcie Paxton, Will Harris, James Hesford, M. Holloway, Emma Mitchel, Frances Rickard, Norman Galbraith, Emma Bhatti, Jenny Edwards, Siobhan Duffy, Fenella Barlow-Pay, Madeline Garcia, Shefali Sangani, Thomas Kneen, Thomas Lee, Angeline Price, Charlotte Davey, S Jones, Kiah Lunstone, A. J. M. Cavenagh, Charlotte Silver, Thomas Telford, Rebecca K. Simmons
Abstract
BACKGROUND: C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality. METHODS: Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell's C statistic and Akaike information criterion (AIC)]. RESULTS: The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable). CONCLUSIONS: The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.